EDWARD PIERS, M. BERT GERAGHTY, R. DEAN SMILLIE, and MARCEL SOUCY. Can. J. Chem. 53,2849 (1975).Stereoselective total syntheses of the tricyclic sesquiterpenoids (-)-copacamphene (1) and (+)-sativene (3) and of the related tetracyclic compounds (-)-cyclocopacamphene (2) and (+)-cyclosativene (4) are described. An efficient four-step synthetic sequence was employed to convert the bicyclic dione 5 into the olefinic ketone 8. The latter compound was converted in four steps into the olefinic alcohol 23. Eliminative cyclization of the corresponding tosylate 25 gave (-)-copacamphene (1) in high yield. In similar fashion, (+)-sativene (3) was obtained by cyclization of the olefinic tosylate 42, which in turn was derived via a four-step synthetic sequence from the olefinic ketone 9. Oxidation of the olefinic alcohol 23 afforded the aldehyde 34. Conversion of the latter compound into the p-tosylhydrazone 35, followed by pyrolysis of the corresponding lithium salt 36, gave the pyrazoline 37. Photolysis of 37 afforded, in high yield, (-)-cyclocopacamphene (2). Similarly, (+)-cyclosativene (4) On decrit des syntheses totales et stCreos6lectives des sesquiterpenoides tricycliques (-) copacamphene (1)et (+) sativene (3)et des composCs t6tracycliques (-) cyclocopacamphene (2) et (+) cyclosativtne (4) qui leur sont relies. On a utilise une sequence de synthtse efficace impliquant 4 Btapes pour transformer la dione 5 en cetone non-saturee 8. On a converti ce dernier compose en alcool olefinique 23 en quatre etapes. L'elimination cyclisante du tosylate correspondant 25 donne le (-) copacamphtne (1) avec un bon rendement. D e la mCme maniere, on obtient le (+) sativene (3) par cyclisation du tosylate non-sature 42, qui derive de la cetone non-saturk 9 par I'intermediaire d'une sequence de synthese en 4 etapes. L'oxydation de I'alcool insature 23 fournit l'aldehyde 34 qui est transforme en p-tosylhydrazone 35. La pyrolyse du sel de lithium de cette derniere (36) donne la pyrazoline 37 qui par photolyse conduit, avec un bon rendement, au (-) cyclocopacamphtne (2). On obtient le (+) cyclosativene (4) de la mCme maniere a partir de I'alcool 41 par I'intermediaire de la pyrazoline 46.

The total synthesis of the racemic modification of the sesquiterpenoid eremophilenolide confirms the structure and stereochemistry assigned to it.

1619(CH,)2CCH,Br -(CH,),C=CH, + B r a (1) (CH,),CCH,Br + O2 -, (CH3),C(OO*)CH2Br (2) propagation reactions. The sensitivity of a n autoxidation to Br. is illustrated by the observation that the oxidizability of 1 is increased by a factor of -100 by the addition of 0.04 A4 HBr.The rate of autoxidation of 1 in the presence of (CH3)3COOH (0.5 to 2 M ) does not depend on the partial pressure of oxygen indicating that reaction 1 is not important in this system. This is not unexpected because a t such large hydroperoxide concentrations any bromine atoms that are formed should undergo chain transfer with the hydroperoxide to regenerate peroxy radicals. (3)This was confirmed by the observation that catalysis of the oxidation of 1 by HBr was eliminated by 2 M (CH3)3COOH (vide Table I).The only rate controlling propagation reaction in this system is, therefore E r -+ (CH,),COOH -HBr + (CH3)3COO* kn' (CH,),COO* + (CH,),CHCH,X -(CH,),COOH + (CH3),CCH2X (4) and the propagation rate constant that is measured is k,'.Measurements of homopropagation rate constants a t 30' for organic substrates with unactivated C-H's (e.g., isobutane 3) and organic substrates with a-bromo and a-chloro substituents (e.g., isopropyl bromide 4 and isopropyl chloride 5 ) is not possible because kinetic chain lengths are too short." A propagation rate constant of 0.003 M-I sec-' for the autoxidation of 3 has, however, been estimated" while rate constants for reaction of 4 and 5 with (CH3)3COO. have been calculated to be -0.0006 A4-I sec-I.l1The reactivity of compounds 1 to 5 to (CH3)3COO. decreases in the order l > 2 -3 > 4 -5 whereas on purely electronic grounds the reactivity order should be 3 > 1 -2 > 4 -5. Thus a CH2Br group activates an adjacent C-H bond relative to a CH3 group because anchimeric assistance from the P-bromine overshadows the deactivating effect expected from electron withdrawal by the bromine. The similarity between the rate constants for 3 and 2 implies that the deactivating effect of a P-chloro substituent is almost exactly balanced by the accelerating effect from anchimeric assistance. W e have previously concludedl * that rate constants for reaction of organic compounds with (CH3)3COO. a t 30' correlate with the strength of the weakest bond in the molecule (D[R-HI) by the empirical equation log ( k p ' / M -i sec-') = 15.4 -0 .2D[R-H]with D[R-HI in kilocalories per mole. As values of k,' for 1 and 2 would be expected to fit this relationship 1 must have a tertiary C-H bond that is -7 kcal mol-' weaker than 4 and -4 kcal mol-' weaker than 3, while the tertiary C-H's in 2 and 3 have approximately the same strength.The estimated stabilizing effect of a CHzBr substituent relative to a CH3 substituent of 4 kcal mol-] is in reasonable agreement with the estimate of 2.5 kcal mol-' obtained by Cain and Solly12 from a kinetic study of the thermolysis of 1 -bromomethyl-and 1 -methyl-4-chlorobicylo[2.-2.01hexanes and the estimate of 3 kcal mol-' made by Skell and SheaI3 from a study of the brominations of l-bromobutane and propane.W e b...

An efficient and highly stereoselective total synthesis of the novel sesquiterpenes (-)-copacamphene (1) and (-)-cyclocopacamphene (3) is described. This work fully corroborates the structure and absolute stereochemistry assigned to the two sesquiterpenes.Une mkthode de synthtse totale, efficace et hautement stkrtosklective de nouveaux sesquiterpenes, le (-)-copacamphtne (1) et le (-)-cyclocopacamphtne (3), est dkrite. Ce travail confirme pleinement la structure et la sttrkochimie absolue attribuke i ces deux sesquiterptnes.

Can. J. Chem. 53,2827. The efficient, stereoselective syntheses of two diastereomeric bicyclo[3.2.1]octadiones (23 and 24) are described and the potential use of these materials for the synthesis of the copa (1-5) and the ylango (7-11) sesquiterpenoids, respectively, is outlined. Conversion of (+)-carvomenthone (26) into the corresponding n-butylthiomethylene derivative 28, followed by alkylation of the latter with ethyl 2-iodopropionate, gave compound 29. Removal of the blocking group from the latter was accompanied by ester hydrolysis and afforded keto acid 30. An efficient intramolecular Claisen condensation of the corresponding ester 31 yielded ( On a transform6 I'octalone connue 39 en cCto-aldehyde 41 par des techniques standards. Le traitement de 41 par du dimethylcuprate de lithium suivi par le piCgeage de I'anion Cnolate qui en rCsulte par du chlorure d'acetyle conduit au compost 42 qui par ozonolyse oxydante fournit le cCto-acide 43. L'estkrification de ce dernier suivie par une conduisation de Claisen intramo-